Open AccessIdentification of Two Novel Frameshift Mutations in Exostosin 1 in Two Families with Multiple Osteochondromas
Author(s) -
Chenyu Wang,
Fei Yu,
JieYuan Jin,
Jiarong He,
LiangLiang Fan,
Juyu Tang,
Rong Xiang
Publication year - 2021
Publication title -
molecular syndromology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.609
H-Index - 36
eISSN - 1661-8777
pISSN - 1661-8769
DOI - 10.1159/000512856
Subject(s) - frameshift mutation , hereditary multiple exostoses , genetics , sanger sequencing , medicine , mutation , gene , biology
Multiple osteochondromas (MO) is an autosomal dominant hereditary disorder, which typically manifests as skeletal dysplasia, mainly involving long bones and knees, ankles, elbows, wrists, shoulders, and pelvis. Previous studies have demonstrated that mutations in exostosin glycosyl transferase-1 ( EXT1 ) and exostosin glycosyl transferase-2 ( EXT2 ) were the main cause of MO. In this study, we enrolled 2 families with MO. Sanger sequencing revealed 2 novel frameshift mutations – c.1432_1433insT; p.Lys479Profs*44 and c.1431_1431delC; p.S478PfsX10 – in the EXT1 gene detected in 2 families, respectively. Both novel mutations, located in the conserved domain of EXT1 and predicted to be disease causing by informatics programs, were absent in our 200 control cohorts and other public databases. Our study expanded the spectrum of EXT1 mutations and contributed to genetic diagnosis and counseling of patients with MO.